PUBLIC ABSTRACT: Freshwater mussels are the most threatened taxonomic group in North America with extinction rates that exceed those of many species found in both terrestrial and freshwater ecosystems including fish, birds, and amphibians. Part of the reason that mussels are so threatened is because their larvae are parasitic on fish, making the completion of their life cycle dependent upon healthy fish populations. The imperilment of freshwater mussels is a cause for concern because of the benefits that mussels provide to freshwater ecosystems including habitat enhancement, substratum stabilization, nutrient cycling, and water clarification. Restoration and conservation efforts targeting western freshwater mussels have been constrained by a lack of information about habitat requirements. As a result, I was interested in investigating how mussel density and distribution varied with respect to both biotic and abiotic factors at multiple spatial scales. I used a modeling approach to determine which habitat parameters were associated with mussel distribution and density throughout a 55-kilometer (km) of the Middle Fork John Day River, Oregon. Parameters included physical stream habitat characteristics, host fish presence, water quality measures, and mussel food quantity and quality. Results of this analysis indicated that mussels responded to the hierarchical arrangement of physical habitat from the valley segment to the channel unit and that higher densities of mussels were found in parts of the river that were more stable at high flows. I found that the distribution of host fish was not limiting to mussels in this river system and that the overall physical habitat characteristics such as gravel size, silt cover, and woody debris were most important to explaining mussel density and distribution. These results will assist mussel restoration efforts by providing specific guidance about the types of habitat conditions that are suitable for mussels at multiple spatial scales.